The pathogenicity of group A streptococci is being studied to gain further insight into the mechanisms of infection and poststreptococcal sequelae. Proposed and continuing projects include the following: A. The structure of M proteins, the protective antigens of group A streptococci, is being studied. New techniques such as detergent extraction are being investigated for obtaining M proteins for further purification. Structural analyses are being carried on to determine the composition and amino acid sequence of M proteins from "rheumatogenic" and "nephritogenic" streptococci. B. The role of secretory antibody in protection against upper respiratory infection by group A streptococci is being investigated by a variety of microserological techniques. The structure of sIgA is being studied with special reference to anti-M properties in secretions of humans receiving M protein vaccines via the intranasal route. C. An in vitro model for the mechanism of rheumatic heart disease is being developed with cultured cardiac myofibers as target cells for lymphocytes "sensitized" to various streptococcal antigens in order to determine the role of cell-mediated immunity in rheumatic heart disease. D. Synthetic lipid bilayers (liposomes) will be prepared with solubilized membrane fractions from streptococcal protoplasts and from sarcolemma of human myocardium. The antigenic specificity of these vesicles will be assessed by release of internal marker with sera known to cross-react with heart and streptococci. Rheumatic fever sera will also be studied in this system.